As all currently available antipsychotics have central D2 antagonism in common, blockade of central D2 receptors (or neuroleptic activity) is generally considered as a pharmacological prerequisite for antipsychotic activity.
Currently available antipsychotics are indeed highly effective against the positive symptoms of schizophrenia (hallucinations, aggression, excitation) but not or to a lesser extent against the affective, depressive and negative symptoms of the disease (although some progress in this respect has been made with the introduction of serotonine-dopamine antagonists such as clozapine, risperidone, olanzapine, etc.). In common practice, antidepressants (predominantly SSRIs) are often co-administered as add-on therapy to neuroleptic treatment, e.g. the majority of schizophrenic patients is treated both with antipsychotics (central D2-antagonists) as well as with antidepressants, predominantly selective serotonin (5-HT) reuptake inhibitors (SSRIs) (see e.g. EP 830 864 A1 by Eli Lilly). SSRIs are a well-known class of antidepressants and useful for the treatment of panic disorders and social phobia.
Furthermore, clinical and pharmacological studies have shown that compounds that show additional 5-HT1A antagonism also show an improved onset of action and are useful in the treatment of a range of affective disorders such as generalised anxiety disorder, panic disorder, obsessive compulsive disorder, depression and aggression. Accordingly, agents acting simultaneously as dopamine D2 and/or D3 antagonists, as SSRIs and as 5-HT1A antagonists may be particularly useful for the treatment of various psychiatric and neurological disorders, in particular certain psychotic disorders, most in particular schizophrenia with improved antipsychotic activity and with an improved antidepressant and/or anxiolytic effect.